We are defining the cells and molecules involved in the regulation of the immune response. In the past year, we have made particular progress in three areas. (1)\In using cloned helper T-cell lines, we have been able to define several distinct functional phenotypes, each having different immunoregulatory effects. This suggests a diversity of function among cells of similar specificity that was not previously suspected. We intend to derive monoclonal antibodies to these cells to determine if they carry unique markers and if we can manipulate the immune response with such antibodies. We have also prepared monoclonal antibodies to the receptor of one such cloned helper T-cell line, which has allowed us to characterize the molecules used by T cells in recognition and to provide an answer to a long-standing mystery, the presence of nonself reactive T cells at high frequency. Our study shows that such cells react with low affinity to a nonself molecule present at high multiplicity using the same receptor that responds to self molecules associated with foreign antigens. (2)\Progress has been made in the preparation of monoclonal antibodies specific for a unique set of immunoregulatory, antigen-specific T-cell proteins. These monoclonal antibodies are useful in in vivo immunomanipulation and for characterizing the molecules involved. (3)\There has been progress in in vitro translation of mRNA encoding such unique T-cell molecules. Using the in vitro translated material that reacts with these monoclonal antibodies and that biologically gives antigen-specific suppression we are cloning cDNA specific for this mRNA, which should allow us to characterize the structure of the molecule as well as the organization of the genomic DNA encoding it. These studies should allow us a clearer picture of the immunoregulatory apparatus that forms the focus of this study. In the coming year, in addition to continuing the studies mentioned above to greater degrees of refinement, we plan to make similar approaches to several other T-cell sets and their molecular products and to improve our assays for immunoregulatory cells and molecules using cloned T-cell lines, monoclonal antibodies, and recombinant DNA technology in this effort. (LB)